title: Histamine and interleukin-2 in acute myelogenous leukemia.
abstract: Interleukin-2 (IL-2) activates natural killer (NK)-cells to destroy leukemic blasts from patients with acute myelogenous leukemia (AML), but even aggressive regimens of IL-2 fail to prevent relapse or prolong remission time in AML. Results obtained in studies of NK-cell-mediated killing of AML blasts show that monocytes inhibit IL-2-induced lysis of AML blasts in vitro. Histamine, a biogenic amine, prevents the monocyte-derived, inhibitory signal; thereby, histamine and IL-2 synergize to induce killing of AML blasts. Here we present updated results of a post-consolidation trial in which histamine (0.5-0.7 mg s.c. bid) has been administered together with IL-2 (1 micro/kg s.c. bid) to 22 AML patients (aged 29-79, mean 59) in repeated courses of three weeks, continued until relapse or until a disease-free remission of 24 months. Low-dose therapy with cytarabine and thioguanine was given between the initial courses of histamine/IL-2. In 13 patients, treatment according to this protocol was started in first complete remission (CR1). The mean remission time in CR1 patients is 19 (median 14) months, and 9/13 remain in CR. Nine patients have entered the protocol in CR2 (n=6), CR3 (n=2), or CR4 (n=1). The mean remission time in CR2-4 is 19 (median 21) months, and 6/9 patients remain in CR. Seven out of seven evaluable patients have achieved a duration of CR which exceeds that of the foregoing remission. Histamine has been well tolerated, and 21/22 CR patients have treated themselves at home throughout the trial. We conclude that the putative benefit of histamine treatment in AML should be the focus of a randomized trial.
authors.affiliation: Department of Virology, Sahlgren's University Hospital, Göteborg, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Hellstrand
authors.forename: U H
authors.initials: UH
authors.lastname: Mellqvist
authors.forename: E
authors.initials: E
authors.lastname: Wallhult
authors.forename: J
authors.initials: J
authors.lastname: Carneskog
authors.forename: E
authors.initials: E
authors.lastname: Kimby
authors.forename: F
authors.initials: F
authors.lastname: Celsing
authors.forename: M
authors.initials: M
authors.lastname: Brune
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002450:Cell Communication; D004357:Drug Synergism; D005260:Female; D006632:Histamine / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007376:Interleukin-2 / Q000502:physiology / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated / Q000502:physiology; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000628:therapy*; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology*; D016896:Treatment Outcome
chemical_list: D007376:Interleukin-2; D006632:Histamine